Loss of stearoyl-CoA desaturase-1 improves insulin sensitivity in lean mice but worsens diabetes in leptin-deficient obese mice

Diabetes. 2007 May;56(5):1228-39. doi: 10.2337/db06-1142. Epub 2007 Mar 16.


The lipogenic gene stearoyl-CoA desaturase (SCD)1 appears to be a promising new target for obesity-related diabetes, as mice deficient in this enzyme are resistant to diet- and leptin deficiency-induced obesity. The BTBR mouse strain replicates many features of insulin resistance found in humans with excess visceral adiposity. Using the hyperinsulinemic-euglycemic clamp technique, we determined that insulin sensitivity was improved in heart, soleus muscle, adipose tissue, and liver of BTBR SCD1-deficient mice. We next determined whether SCD1 deficiency could prevent diabetes in leptin-deficient BTBR mice. Loss of SCD1 in leptin(ob/ob) mice unexpectedly accelerated the progression to severe diabetes; 6-week fasting glucose increased approximately 70%. In response to a glucose challenge, Scd1(-/-) leptin(ob/ob) mice had insufficient insulin secretion, resulting in glucose intolerance. A morphologically distinct class of islets isolated from the Scd1(-/-) leptin(ob/ob) mice had reduced insulin content and increased triglycerides, free fatty acids, esterified cholesterol, and free cholesterol and also a much higher content of saturated fatty acids. We believe the accumulation of lipid is due to an upregulation of lipoprotein lipase (20-fold) and Cd36 (167-fold) and downregulation of lipid oxidation genes in this class of islets. Therefore, although loss of Scd1 has beneficial effects on adiposity, this benefit may come at the expense of beta-cells, resulting in an increased risk of diabetes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Gene Expression Regulation, Enzymologic
  • Glucose Clamp Technique
  • Glucose Tolerance Test
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / cytology
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / physiology*
  • Leptin / deficiency*
  • Leptin / genetics
  • Lipoprotein Lipase / metabolism
  • Mice
  • Mice, Knockout
  • Polymerase Chain Reaction
  • Stearoyl-CoA Desaturase / deficiency
  • Stearoyl-CoA Desaturase / genetics
  • Stearoyl-CoA Desaturase / metabolism*
  • Thinness


  • Blood Glucose
  • Insulin
  • Leptin
  • Stearoyl-CoA Desaturase
  • Lipoprotein Lipase